The A1C assay, expressed as the percent of hemoglobin that is glycated, measure chronic glycemia and is widely used to judge the adequacy of diabetes treatment an adjust therapy. Day-to-day management is guided by self-monitoring of capillary glucose concentrations(milligrams per deciliter or millimoles per liter), e.g., see Nathan et al., “Translating the A1C Assay Into Estimated Average Glucose Values” Diabetes Care, Vol. 31, No. 8, August, 2008, which is hereby incorporated herein, in its entirety, by reference thereto. Chronic glycemia, commonly characterized by average glucose levels in a patient and therefore denoted AG, is the persistent mean level of blood glucose (BG) over a threshold value and over an extended period of multiple days and is related to diabetes progression and complications. The threshold level may vary among different treatment regimens, but is generally a glucose level higher than 11.1 mmol/l (200 mg/dl). Reference ranges for blood tests are 11.1 mmol/l, but symptoms may not start to become noticeable until even higher values such as 250-300 mg/dl or 15-20 mmol/l. A subject with a consistent range between 100 and 126 (American Diabetes Association guidelines) is considered hyperglycemic, while above 126 mg/dl or 7 mmol/l is generally held to have diabetes. Chronic levels exceeding 7 mmol/l (125 mg/dl) can produce organ damage. Controlling chronic glycemia is a key factor in the clinical management of diabetes healthcare as described in established medical reference books, e.g., see International Diabetes Center, Staged Diabetes Management, John Wiley & Sons, 2006, p. 13 and The Art and Science of Diabetes Self-Management Education, American Association of Diabetes Educators, 2006, pp 145, 218, both of which are hereby incorporated herein, in their entireties, by reference thereto.
The fraction or percent of glycated hemoglobin, denoted HbA1C or A1C, is currently used to infer the level of AG with a standard error ranging from ±10 to ±25 mg/dL, e.g., see Nathan et al., “Translating the A1C Assay Into Estimated Average Glucose Values” Diabetes Care, Vol. 31, No. 8, August, 2008, and Kahn et al., “Translating the A1C Assay”, diabetes Care, Vol. 31, No. 8, August, 2008, both of which are hereby incorporated herein, in their entireties, by reference thereto.
However, as described in recent publications, the significant impact of personal factors on the association of A1C with chronic glycemia compromises this inference, e.g., see Cohen et al., “Red cell life span heterogenicity in hematologically normal people is sufficient to alter HbA1c”, Blood, 15 Nov. 2008, Vol. 112, No. 10, PP 4284-4291 and Wilson et al., “Persistence of Individual Variations in Glycated Hemoglobin”, Diabetes Care, Vol. 34, June 2011, pp 1315-1317, both of which are hereby incorporated herein, in their entireties, by reference thereto. Despite newer methods that correct for some personal factors A1C is still an inherently slow measure of chronic glycemia requiring typically 3 months to fully equilibrate and hence is insensitive to immediate important trends.
There is a need for timelier diagnostics to directly track chronic glycemia with better precision based on casual patient data, typically collected at self-monitoring-blood-glucose (SMBG) events.
There is a need for timelier diagnostics that can capture and be used to identify long-term (gradient) trends in the diabetic status specific to each patient.
It would further be desirable to provide timelier diagnostic capabilities as incorporated into a device to perform the diagnostic or in devices such as blood glucose monitoring devices currently used by patients and doctors.